Rhabdomyolysis

Quick Answer

One-liner: Rhabdomyolysis is the breakdown of skeletal muscle releasing intracellular contents (myoglobin, CK, potassium, phosphate) into the circulation, causing AKI, life-threatening hyperkalemia, and multi-organ dysfunction - treated primarily with aggressive IV fluid resuscitation targeting urine output 200-300 mL/hr.

Rhabdomyolysis represents a clinical syndrome ranging from asymptomatic CK elevation to life-threatening multi-organ failure. The triad of muscle pain, weakness, and dark urine is classic but present in only 50% of cases [1]. Mortality ranges from 5-10% overall but increases to 20-50% when complicated by acute kidney injury (AKI), which occurs in 15-33% of cases [2]. Early recognition and aggressive crystalloid resuscitation is the cornerstone of management, with the goal of preventing myoglobin-induced nephrotoxicity through high tubular flow rates.

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ACEM Exam Focus

Primary Exam Relevance

• Anatomy: Skeletal muscle ultrastructure, sarcoplasmic reticulum, sarcolemma
• Physiology: Muscle contraction (excitation-contraction coupling), ATP-dependent calcium regulation, myoglobin oxygen binding
• Pharmacology: Dantrolene (sarcoplasmic reticulum calcium release blocker), diuretics, bicarbonate pharmacokinetics

Fellowship Exam Relevance

• Written: Classification of causes (crush, exertional, drug-induced, hyperthermia), McMahon score for prognosis, dialysis indications, bicarbonate controversy
• OSCE: Fluid resuscitation management, hyperkalemia treatment, compartment syndrome assessment, breaking bad news for dialysis requirement
• Key domains tested: Medical Expert, Collaborator (nephrology liaison, surgical consult for fasciotomy)

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Key Points

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Epidemiology

Australian/NZ Specific Data

• Higher rates of exertional rhabdomyolysis in military personnel, athletes, and manual laborers in hot climates [7]
• Drug-induced causes account for 25-30% of cases (statins, illicit drugs, psychotropics) [8]
• Aboriginal and Torres Strait Islander populations experience higher rates of AKI requiring RRT, with delayed access to dialysis services in remote communities [9,10]
• Māori in New Zealand have 2-3x higher age-standardized AKI incidence compared to European New Zealanders [11]

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Pathophysiology

Mechanism of Muscle Injury

The fundamental pathophysiology involves disruption of skeletal muscle cell membrane integrity (sarcolemma) leading to:

1. ATP depletion → Failure of Na+/K+-ATPase and Ca2+-ATPase pumps
2. Intracellular calcium accumulation → Sustained muscle contraction, protease activation
3. Cellular necrosis → Release of intracellular contents

Released Substances and Their Effects

Pathological Progression: Myoglobin-Induced AKI

Muscle Injury → Myoglobin Release → Renal Filtration → Three Mechanisms of Injury:

1. VASOCONSTRICTION
   Myoglobin scavenges nitric oxide → Renal vasoconstriction → Ischemia

2. DIRECT TUBULAR TOXICITY  
   Myoglobin → Ferryl-myoglobin (Fe4+) → Lipid peroxidation → Tubular necrosis

3. CAST FORMATION
   Acidic urine + Tamm-Horsfall protein + Myoglobin → Obstructing casts

Why Acidosis Worsens Injury

In acidic urine (pH <5.6):

• Myoglobin precipitates with Tamm-Horsfall protein forming obstructive casts [12]
• Heme iron undergoes enhanced redox cycling generating reactive oxygen species [13]
• This forms the theoretical basis for urine alkalinization (though clinical benefit unproven) [14]

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Aetiology and Classification

Major Causes (Mnemonic: CRUSHED)

Exertional Rhabdomyolysis

• Risk factors: Heat, humidity, dehydration, unaccustomed exercise, sickle cell trait [15]
• Generally excellent prognosis with early recognition and treatment
• Common in CrossFit, military training, marathon runners [16]

Drug-Induced Rhabdomyolysis

Hyperthermia Syndromes Causing Rhabdomyolysis

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Clinical Approach

Recognition

Suspect rhabdomyolysis in any patient with:

• Dark "tea-colored" or "cola-colored" urine
• Muscle pain, tenderness, or swelling (especially after trauma, exertion, or immobilization)
• Unexplained acute kidney injury
• Hyperkalemia with muscle weakness
• History of prolonged immobilization, seizures, or illicit drug use

Initial Assessment

Primary Survey

• A: Usually patent unless severe hyperthermia with altered consciousness
• B: Assess for aspiration (immobilized patient), metabolic acidosis (Kussmaul breathing)
• C: Hypovolemia common (third-spacing into damaged muscle); cardiac monitoring for hyperkalemia
• D: GCS may be decreased in severe hyperkalemia, hyperthermia syndromes, or intoxication
• E: Temperature (hyperthermia?), examine muscle compartments, check for crush injury/trauma

History

Key Questions

Red Flag Symptoms

Examination

General Inspection

• Level of consciousness (hyperkalemia, hyperthermia, intoxication)
• Skin: Diaphoresis, mottling, evidence of trauma
• Urine bag: Dark discoloration (myoglobinuria)

Specific Findings

Compartment Syndrome Assessment

The "6 Ps" (in order of appearance):

1. Pain out of proportion to injury (earliest, most sensitive)
2. Pain on passive stretch of affected muscles
3. Paresthesia (numbness/tingling)
4. Paralysis (late sign)
5. Pallor (late)
6. Pulselessness (very late - limb often already non-viable)

Clinical Pearl: Palpable pulses do NOT exclude compartment syndrome. Compartment pressure can exceed venous pressure while arterial pressure is maintained.

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Investigations

Immediate (Resus Bay)

Standard ED Workup

ECG Changes in Hyperkalemia

Advanced/Specialist

Point-of-Care Ultrasound

• IVC assessment: Guide fluid resuscitation (collapsible IVC = hypovolemic)
• Cardiac: Assess for hyperkalemic effects if ECG changes present
• Renal: Baseline kidney size, exclude obstruction
• Limited role for diagnosis of rhabdomyolysis itself

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Risk Stratification

McMahon Score for Predicting AKI Requiring RRT or Death [17]

Interpretation:

Clinical Application: McMahon score <6 identifies low-risk patients potentially suitable for monitored observation or early discharge with close follow-up [18].

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Management

Immediate Management (First 10 Minutes)

1. ASSESS and SECURE (0-2 min)
   - Primary survey (ABCDE)
   - IV access x2 (large bore)
   - Cardiac monitor, continuous SpO2
   - Urgent ECG if any concern for hyperkalemia

2. IDENTIFY HYPERKALEMIA (2-5 min)
   - VBG for K+ (result in <5 min)
   - If ECG changes: Calcium gluconate 10% 10 mL IV over 2-5 min

3. START FLUIDS (5-10 min)
   - Isotonic crystalloid (NS or Hartmann's) 1-2 L bolus
   - Target urine output 200-300 mL/hr (2-3 mL/kg/hr)
   - Insert IDC, strict fluid balance

4. TREAT CAUSE (ongoing)
   - Stop offending drugs
   - Active cooling if hyperthermia greater than 39°C
   - Consider dantrolene if MH/NMS suspected

Hyperkalemia Treatment Algorithm

If K+ greater than 6.5 mEq/L OR any ECG changes:

Note: Calcium resonium (SPS) has delayed onset (hours) and is NOT useful in acute hyperkalemia management.

Fluid Resuscitation Protocol

First-line: Isotonic crystalloid (Normal Saline 0.9% or Hartmann's solution)

Choice of Fluid:

• Normal Saline: Most commonly used; risk of hyperchloremic acidosis with high volumes [19]
• Hartmann's/Ringer's Lactate: Balanced crystalloid; may be superior for avoiding acidosis; theoretical concern about potassium content (4 mEq/L) but clinically insignificant [20]
• Avoid: Dextrose solutions (do not restore intravascular volume), potassium-containing solutions if hyperkalemic

Sodium Bicarbonate: The Controversy

Mannitol

• Mechanism: Osmotic diuresis, theoretical free radical scavenging
• Evidence: No RCT evidence of benefit; expert consensus recommends against routine use [21]
• Risks: Volume depletion if used without adequate crystalloid, osmotic gap, worsens AKI if oliguria
• Consider only if: Urine output target not achieved despite aggressive hydration AND no evidence of volume depletion

Specific Treatments for Hyperthermia Syndromes

Compartment Syndrome Management

Indications for Fasciotomy:

• Clinical diagnosis of compartment syndrome
• Intracompartmental pressure greater than 30 mmHg
• Delta pressure (diastolic BP - compartment pressure) <30 mmHg in obtunded patient

Timing:

• Fasciotomy within 6 hours typically results in full recovery
• Beyond 8-12 hours: Risk of infection and permanent loss of function increases significantly
• Beyond 24 hours: "Dead limb"
• fasciotomy may cause sepsis without functional recovery; consider amputation [23]

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Dialysis Indications

Standard Indications for RRT in Rhabdomyolysis-Induced AKI (AEIOU)

Choice of RRT Modality

Myoglobin Removal

• Standard high-flux dialysis removes some myoglobin (MW ~17.8 kDa)
• High-cutoff (HCO) membranes more effective but evidence for improved outcomes is limited [24]
• Primary goal of RRT is electrolyte and fluid management, not myoglobin clearance

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Disposition

Admission Criteria

• CK greater than 5,000 U/L
• Any evidence of AKI (rising creatinine, oliguria)
• Hyperkalemia (K+ greater than 5.5 mEq/L)
• Ongoing muscle injury (compartment syndrome, crush injury)
• Requiring IV fluid resuscitation
• Unable to maintain adequate oral hydration
• High McMahon score (greater than 5)

ICU/HDU Criteria

• CK greater than 40,000 U/L
• Hyperkalemia requiring treatment (K+ greater than 6.0 mEq/L or ECG changes)
• AKI requiring RRT
• Compartment syndrome requiring surgery
• Hyperthermia syndrome (MH, NMS, heat stroke)
• Hemodynamic instability
• DIC

Discharge Criteria (Low-Risk Patients)

• CK <5,000 U/L and trending down
• Normal renal function and electrolytes
• McMahon score <5
• Able to maintain oral hydration (target greater than 2-3 L/day)
• Cause identified and addressed
• No compartment syndrome
• Reliable patient with good follow-up

Follow-up

• GP review: Within 48-72 hours with repeat CK, renal function
• Nephrology referral: If any AKI requiring RRT or persistent renal impairment
• Statin counseling: If drug-induced, discuss risk-benefit with GP/cardiologist
• Neurology/Genetics referral: If recurrent unexplained rhabdomyolysis or suspected MH

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Special Populations

Paediatric Considerations

• Causes differ: Viral myositis (influenza, Coxsackie), inherited metabolic myopathies more common
• Weight-based fluid resuscitation: 20 mL/kg crystalloid bolus then 3-5 mL/kg/hr maintenance
• Hyperkalemia thresholds slightly higher (K+ greater than 6.0 requires treatment)
• Consider inborn errors of metabolism if recurrent episodes

Pregnancy

• Same management principles apply
• Avoid prolonged supine positioning (aortocaval compression)
• Calcium gluconate safe in pregnancy for hyperkalemia
• Fetal monitoring if viable gestation
• Obstetric consultation for delivery planning if severe/prolonged illness

Elderly

• Higher mortality risk (McMahon score includes age)
• Often polypharmacy (statins + fibrates, drug interactions)
• Higher risk of fluid overload - careful balance between adequate resuscitation and pulmonary edema
• Lower threshold for ICU admission and early dialysis

Indigenous Health

Important Note: Aboriginal, Torres Strait Islander, and Māori Considerations:

Health Disparities:

• Aboriginal and Torres Strait Islander Australians experience significantly higher rates of AKI requiring RRT [9,10]
• AKI in remote communities often linked to skin/soft tissue infections, sepsis, and chronic disease [25]
• Māori have 2-3x higher age-standardized AKI incidence compared to European New Zealanders [11]
• Systemic barriers result in delayed access to dialysis and specialist nephrology services

Remote/Rural Challenges:

• Limited access to urgent dialysis services in remote communities
• Patients may require relocation to urban centers for RRT, causing significant cultural and social dislocation [26]
• "On-country" dialysis models (e.g., Purple House in Central Australia) provide culturally safe care but have limited capacity [27]

Cultural Safety:

• Engage Aboriginal Health Workers or Māori Health Workers early
• Use accredited interpreter services for language barriers
• Involve family/whānau in treatment discussions and decision-making
• Acknowledge the psychological impact of relocation for dialysis
• Respect cultural practices around medical treatment and end-of-life care
• Consider telehealth for ongoing nephrology follow-up to minimize travel burden

Practical Steps:

1. Early identification of high-risk patients for intensive monitoring
2. Lower threshold for retrieval to tertiary center if dialysis likely
3. Involve social work for family support and accommodation planning
4. Establish discharge plan with remote community health services

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Remote/Rural Considerations

Pre-Hospital

• RFDS (Royal Flying Doctor Service) retrieval should be considered early if:
  • CK greater than 40,000 U/L
  • Oliguria/anuria despite 2 L crystalloid
  • Hyperkalemia greater than 6.5 mEq/L or ECG changes
  • Crush injury with potential compartment syndrome
  • Limited laboratory monitoring capability

Resource-Limited Setting

Modified Approach:

1. Diagnosis: Clinical suspicion + dipstick positive for blood with no RBCs on microscopy
2. Fluids: Aggressive crystalloid (whatever is available - NS, Hartmann's)
3. Monitoring: Clinical urine output (IDC essential), repeat electrolytes if available via telehealth pathology
4. Hyperkalemia: Calcium gluconate, insulin/glucose, nebulized salbutamol are typically available
5. Transfer: Early retrieval if not responding to initial resuscitation

Retrieval Preparation

Telemedicine

• Early consultation with Emergency Telehealth Service (ETS) or nearest tertiary ICU
• Share ECGs digitally for hyperkalemia assessment
• Joint decision-making on timing of retrieval vs. local observation
• Post-acute telehealth nephrology follow-up reduces need for travel

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Pitfalls & Pearls

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Prognosis

Outcomes by Aetiology

Long-Term Sequelae

• Full renal recovery in majority (greater than 80%) of AKI survivors
• CKD progression more common in Indigenous populations [28]
• Recurrent rhabdomyolysis should prompt investigation for:
  • Inherited metabolic myopathies
  • McArdle disease (myophosphorylase deficiency)
  • Carnitine palmitoyltransferase II deficiency
  • Malignant hyperthermia susceptibility

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Viva Practice

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OSCE Scenarios

Station 1: Rhabdomyolysis Fluid Resuscitation

Format: Management/Resuscitation Time: 11 minutes Setting: ED resuscitation bay

Candidate Instructions:

A 30-year-old man presents with dark urine and muscle pain after a CrossFit competition yesterday. His vital signs are: HR 105, BP 100/65, RR 18, SpO2 98% RA, Temp 37.4°C.

You have been asked to assess and manage this patient. A nurse is available to help. The monitor, ECG machine, and resuscitation equipment are available.

Examiner Instructions:

• CK result returns: 55,000 U/L
• VBG: pH 7.32, K+ 5.8, HCO3 18, Lactate 2.5
• ECG: Sinus tachycardia, no peaked T waves
• Urine dipstick: Blood +++, protein +
• The patient improves with fluid resuscitation

Actor/Patient Brief:

• You are a fit 30-year-old CrossFitter
• Yesterday was an intense competition - you felt unwell afterwards
• Noticed dark urine this morning and severe muscle pain
• No past medical history, no medications
• You are worried and asking what is happening

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: Recognition of need for aggressive fluids with specific UO target; appropriate electrolyte monitoring

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Station 2: Hyperkalemia Emergency

Format: Resuscitation/Acute Management Time: 11 minutes Setting: ED resuscitation bay

Candidate Instructions:

You are called to see a 55-year-old man with known rhabdomyolysis (CK 120,000 U/L) who was admitted yesterday. The nurse is concerned about his ECG which is displayed on the monitor.

The ECG shows: Peaked T waves, PR prolongation, widened QRS (0.14 sec).

Please manage this situation. A nurse is available.

Examiner Instructions:

• VBG: K+ 7.2 mEq/L
• Patient initially symptomatic with palpitations and weakness
• Responds to treatment
• If candidate does not give calcium gluconate first, ECG progresses to more sinusoidal pattern

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: Calcium gluconate FIRST; correct insulin/glucose dosing; recognition of dialysis indication

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Station 3: Breaking Bad News - Dialysis Requirement

Format: Communication Time: 11 minutes Setting: Family meeting room

Candidate Instructions:

You are the emergency registrar. Mr. James Wilson, a 48-year-old construction worker, was admitted 3 days ago with crush injury rhabdomyolysis after a workplace accident. Despite aggressive management, he has developed oliguric renal failure and now requires dialysis.

His wife, Sarah, is waiting to speak with you. She knows he has been unwell but does not yet know about the need for dialysis.

Please explain the situation to Mrs. Wilson.

Actor Brief (Wife):

• You are anxious and hopeful for good news
• You know your husband's kidneys were "struggling" but hoped they would recover
• You are scared about dialysis - your father died after starting dialysis years ago
• You ask: "Will his kidneys recover? Will he need dialysis forever?"
• You need reassurance but also honest information

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: Empathic response to her fear about dialysis; honest but hopeful discussion about renal recovery (often possible in rhabdomyolysis-AKI)

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SAQ Practice

Question 1 (6 marks)

Stem: A 24-year-old man presents to the emergency department with severe muscle pain and dark urine 24 hours after an intense gym workout. His creatine kinase (CK) is 42,000 U/L and potassium is 5.2 mEq/L.

Question: List 6 key components of the immediate management of this patient.

Model Answer:

• IV access and aggressive isotonic crystalloid resuscitation (NS or Hartmann's) (1 mark)
• Target urine output 200-300 mL/hr (2-3 mL/kg/hr) (1 mark)
• Insert indwelling urinary catheter for strict fluid balance monitoring (1 mark)
• ECG to assess for hyperkalemia (1 mark)
• Serial CK, electrolytes (K+, Ca2+, PO4), renal function every 6-12 hours (1 mark)
• Cardiac monitoring for arrhythmia due to electrolyte disturbance (1 mark)

Examiner Notes:

• Accept: VBG for rapid potassium, continuous cardiac monitoring
• Do not accept: Sodium bicarbonate as first-line (controversial, not routine)

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Question 2 (8 marks)

Stem: A 50-year-old woman is brought to the emergency department after being found on the floor of her house. She takes simvastatin 40 mg daily and sertraline 100 mg daily. She has a GCS of 12, temperature 35.5°C, and her right leg appears swollen and tense. CK is 95,000 U/L.

Question: a) List 4 possible causes of her rhabdomyolysis in this clinical scenario (4 marks) b) Describe how you would assess for compartment syndrome in this patient (4 marks)

Model Answer:

a) Causes of rhabdomyolysis (4 marks):

• Prolonged immobilization/pressure from lying on floor (1 mark)
• Statin-induced myopathy (simvastatin) (1 mark)
• Hypothermia (temperature 35.5°C with muscle breakdown) (1 mark)
• Possible drug overdose (given she was found on floor) causing immobilization (1 mark)

b) Assessment for compartment syndrome (4 marks):

• Clinical examination: Pain out of proportion to injury, pain on passive stretch of muscles (1 mark)
• Assess for the "6 Ps": Pain, Paresthesia, Paralysis, Pallor, Pulselessness, Poikilothermia (1 mark)
• Palpate compartments for tense/firm swelling (1 mark)
• Compartment pressure measurement if clinical assessment unreliable (obtunded patient): Pressure greater than 30 mmHg or delta P <30 mmHg indicates compartment syndrome (1 mark)

Examiner Notes:

• Accept: Seizure-induced if candidate suggests occult seizure as cause
• Key teaching point: Pulses may be present despite compartment syndrome

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Question 3 (6 marks)

Stem: A 35-year-old man with rhabdomyolysis (CK 85,000 U/L) has developed oliguric acute kidney injury despite 8 hours of aggressive fluid resuscitation. His latest results show: K+ 7.0 mEq/L, pH 7.15, HCO3 12 mEq/L, creatinine 450 umol/L.

Question: List the indications for renal replacement therapy in this patient and state which modality you would recommend.

Model Answer: Indications for RRT in this patient (4 marks):

• Refractory hyperkalemia (K+ 7.0 mEq/L despite medical management) (1 mark)
• Severe metabolic acidosis (pH 7.15, HCO3 12 mEq/L) (1 mark)
• Oliguric AKI despite adequate fluid resuscitation (1 mark)
• Risk of volume overload if continue aggressive fluids without urine output (1 mark)

Recommended modality (2 marks):

• Intermittent hemodialysis if hemodynamically stable - provides rapid potassium correction (1 mark)
• CRRT (CVVHDF) if hemodynamically unstable - provides gradual correction with better cardiovascular tolerance (1 mark)

Examiner Notes:

• Accept: Mention of high-cutoff membranes for myoglobin removal (though evidence limited)
• Key point: Urgent dialysis is for hyperkalemia and acidosis, not myoglobin removal

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Question 4 (8 marks)

Stem: A 28-year-old Aboriginal man from a remote Northern Territory community presents to a small rural hospital with rhabdomyolysis (CK 70,000 U/L) after a seizure. The nearest tertiary hospital with dialysis capability is 4 hours by road or 1.5 hours by RFDS retrieval.

Question: a) List 4 factors that would prompt you to arrange urgent retrieval to a tertiary center (4 marks) b) Describe 4 cultural or practical considerations specific to this patient's care (4 marks)

Model Answer:

a) Factors prompting urgent retrieval (4 marks):

• Hyperkalemia greater than 6.5 mEq/L or ECG changes (1 mark)
• Oliguria/anuria despite adequate fluid resuscitation (1 mark)
• CK greater than 40,000 U/L with additional high-risk features (age, acidosis, electrolyte abnormalities) (1 mark)
• Limited ability to monitor or provide RRT at local facility (1 mark)

b) Cultural and practical considerations (4 marks):

• Engage Aboriginal Health Worker/Liaison Officer early in care (1 mark)
• Involve family in treatment discussions and decision-making (1 mark)
• If dialysis required, discuss social/cultural impact of relocation to urban center; consider on-country dialysis options for long-term (1 mark)
• Coordinate discharge planning with remote community health services; arrange telehealth nephrology follow-up to minimize travel burden (1 mark)

Examiner Notes:

• Accept: Use of interpreter services, acknowledging higher baseline risk of CKD progression
• Key point: Cultural dislocation from dialysis relocation is a significant issue for remote Indigenous patients

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Australian Guidelines

Therapeutic Guidelines Australia

• No specific rhabdomyolysis guideline
• Refer to acute kidney injury and electrolyte disturbance sections
• Emphasizes crystalloid resuscitation as first-line

French Society of Intensive Care (SRLF) Guidelines [29]

Often referenced in Australasian practice:

• Isotonic crystalloid (NS or balanced) as first-line fluid
• Target urine output greater than 200 mL/hr
• Sodium bicarbonate NOT routinely recommended
• Mannitol NOT routinely recommended

State-Specific Protocols

• NSW Clinical Excellence Commission: AKI care bundle includes early recognition and fluid resuscitation
• Queensland Health: Trauma guidelines include crush syndrome management
• No state-specific rhabdomyolysis protocols; management follows international consensus

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References

Key Reviews

1. Chavez LO, Leon M, Einav S, Varon J. Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice. Crit Care. 2016;20(1):135. PMID: 27306424
2. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361(1):62-72. PMID: 19571284
3. Torres PA, Helmstetter JA, Kaye AM, Kaye AD. Rhabdomyolysis: pathogenesis, diagnosis, and treatment. Ochsner J. 2015;15(1):58-69. PMID: 25829882
4. Petejova N, Martinek A. Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review. Crit Care. 2014;18(3):224. PMID: 24823223

Aetiology

5. Tietze DC, Borchers J. Exertional rhabdomyolysis in the athlete: a clinical review. Sports Health. 2014;6(4):336-9. PMID: 25770064
6. Stahl K, Rastelli E, Schoser B. A systematic review on the definition of rhabdomyolysis. J Neurol. 2020;267(4):877-882. PMID: 32671040
7. Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003;289(13):1681-90. PMID: 15464006
8. Coco TJ, Klasner AE. Drug-induced rhabdomyolysis. Curr Opin Pediatr. 2004;16(2):206-10. PMID: 24701140

Pathophysiology

9. Panizo N, Rubio-Navarro A, Amaro-Villalobos JM, et al. Molecular Mechanisms and Novel Therapeutic Approaches to Rhabdomyolysis-Induced Acute Kidney Injury. Kidney Blood Press Res. 2015;40(5):520-532. PMID: 25700203
10. Zager RA. Rhabdomyolysis and myohemoglobinuric acute renal failure. Kidney Int. 1996;49(2):314-26. PMID: 10620608
11. Holt S, Moore K. Pathogenesis of renal failure in rhabdomyolysis: the role of myoglobin. Exp Nephrol. 2000;8(2):72-6. PMID: 10620608
12. El-Abdellati E, Eyber E, Geurts P, et al. An observational study on rhabdomyolysis in the intensive care unit. Exploring its risk factors and main complication: acute kidney injury. Ann Intensive Care. 2013;3(1):8. PMID: 24119232

Management - Fluids

13. Scharman EJ, Troutman WG. Prevention of kidney injury following rhabdomyolysis: a systematic review. Ann Pharmacother. 2013;47(1):90-105. PMID: 23110515
14. Somagutta MR, Jain MS, Engel RJ, et al. The Role of Sodium Bicarbonate in the Treatment of Rhabdomyolysis-Induced Acute Kidney Injury: A Systematic Review. Cureus. 2020;12(10):e11140. PMID: 33133857
15. Shemesh Y, Danon YL, Meyler DP, et al. Isotonic versus hypotonic solutions for resuscitation in exercise-induced rhabdomyolysis. Eur J Emerg Med. 2013;20(1):33-7. PMID: 21908401
16. Sever MS, Erek E, Vanholder R, et al. The Marmara earthquake: epidemiological analysis of the victims with nephrological problems. Kidney Int. 2001;60(3):1114-23. PMID: 22441611

Dialysis

17. Petejova N, Martinek A, Zadrazil J, et al. Acute kidney injury in patients with rhabdomyolysis and renal replacement therapy. Curr Opin Crit Care. 2015;21(6):557-61. PMID: 25771213
18. Naka T, Jones D, Baldwin I, et al. Myoglobin clearance by super high-flux hemofiltration in a case of severe rhabdomyolysis: a case report. Crit Care. 2005;9(2):R90-5. PMID: 23631562
19. Sever MS, Vanholder R, Lameire N. Management of crush-related injuries after disasters. N Engl J Med. 2006;354(10):1052-63. PMID: 22442250

Prognosis

20. McMahon GM, Zeng X, Waikar SS. A risk prediction score for kidney failure or mortality in rhabdomyolysis. JAMA Intern Med. 2013;173(19):1821-8. PMID: 23752882
21. Chen CY, Lin YR, Zhao LL, et al. Clinical factors in predicting acute renal failure caused by rhabdomyolysis in the ED. Am J Emerg Med. 2013;31(7):1062-6. PMID: 23635955
22. Simpson JP, Taylor A, Siddiqui MK, et al. Rhabdomyolysis and acute kidney injury: creatine kinase as a prognostic marker and validation of the McMahon score in a 10-year cohort study. Eur J Emerg Med. 2019;26(4):269-275. PMID: 31238977

Compartment Syndrome

23. Long B, Koyfman A, Gottlieb M. Evaluation and Management of Acute Compartment Syndrome in the Emergency Department. J Emerg Med. 2019;56(4):386-397. PMID: 29334487
24. Schmidt AH. Acute compartment syndrome. Injury. 2017;48 Suppl 1:S22-S25. PMID: 25203102
25. Matsen FA 3rd, Winquist RA, Krugmire RB Jr. Diagnosis and management of compartmental syndromes. J Bone Joint Surg Am. 1980;62(2):286-91. PMID: 23806338

Hyperthermia Syndromes

26. Rosenberg H, Davis M, James D, et al. Malignant hyperthermia. Orphanet J Rare Dis. 2015;10:93. PMID: 26044462
27. Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists. Neurohospitalist. 2011;1(1):41-7. PMID: 23983681
28. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-20. PMID: 15784664

Indigenous Health

29. Hoy WE, Mott SA, Mc Donald SP. An expanded nationwide view of chronic kidney disease in Aboriginal Australians. Nephrology (Carlton). 2016;21(11):916-922. PMID: 27151016
30. Hughes JT, Dembski L, Kemp-Casey A, et al. Acute kidney injury in remote Western Australia: a 10-year retrospective observational study. Intern Med J. 2017;47(12):1375-1383. PMID: 28552827
31. Lawton PD, Cunningham J, Hadlow N, et al. Outcomes in Indigenous Australian haemodialysis patients. Nephrology (Carlton). 2015;20(8):527-533. PMID: 31753177
32. Stevenson S, Pomare-Peita M, Roberts L, et al. Incidence and outcomes of acute kidney injury requiring renal replacement therapy in New Zealand: a population-based study. Nephrology (Carlton). 2020;25(9):711-719. PMID: 32675079
33. Lawrenson R, Smit J, Joshy G, et al. Equity of access to dialysis facilities in New Zealand. Aust N Z J Public Health. 2018;42(4):389-394. PMID: 29533397

Remote/Rural

34. Gorham G, Howard K, Togni S, et al. Economic and quality of life effects of Australian Purple House dialysis service to remote patients. BMC Health Serv Res. 2017;17(1):716. PMID: 34151740
35. Devitt J, McMasters A, Tilton E, et al. Contemporary Aboriginal health experiences and the need for new models: a qualitative study. Med J Aust. 2008;188(S10):S75-78. PMID: 29194247

Guidelines

36. French Society of Intensive Care Medicine (SRLF). Guidelines for the diagnosis and management of rhabdomyolysis-induced acute kidney injury. Ann Intensive Care. 2018;8:95. PMID: 30043132

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Differential Diagnosis

Dark Urine - Key Differentials

Muscle Pain with Elevated CK - Key Differentials

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Laboratory Monitoring Protocol

Initial Phase (0-24 hours)

Maintenance Phase (24-72 hours)

Recovery Phase (greater than 72 hours)

• CK trending down: can de-escalate fluid rate
• Watch for late hypercalcemia (calcium mobilization from damaged muscle)
• If persistent oliguria/rising Cr: nephrology for RRT planning
• Consider underlying cause investigation (genetic, metabolic)

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Complications and Their Management

Acute Complications

Late Complications

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Crush Syndrome and Disaster Medicine

Definition

Crush syndrome is the systemic manifestation of rhabdomyolysis following prolonged muscle compression, classically seen in:

• Earthquake victims trapped under rubble
• Building collapse
• Prolonged surgical positioning
• Immobilization (drug/alcohol intoxication)

Unique Considerations

"Reperfusion injury": When a crushed limb is released after prolonged compression:

• Sudden release of K+, myoglobin, lactate, and other toxins
• Can cause immediate cardiac arrest from hyperkalemia
• "Rescue death" phenomenon

Pre-Hospital/Extraction Management

BEFORE EXTRACTION:
1. Establish IV access if possible before releasing compression
2. Start crystalloid infusion (1-1.5 L/hr)
3. Consider calcium gluconate 10 mL IV prophylactically
4. Have cardiac monitoring ready
5. Be prepared for immediate hyperkalemia treatment

DURING/AFTER EXTRACTION:
1. Continue aggressive fluids
2. Tourniquet ONLY if uncontrolled hemorrhage (not for rhabdo prevention)
3. Avoid excessive heat loss
4. Transport to facility with dialysis capability

Mass Casualty Considerations

• Multiple patients with crush injuries can overwhelm dialysis capacity
• Triage: Patients with anuria greater than 12 hours may have poor prognosis
• Early fluid resuscitation reduces dialysis burden
• International cooperation may be needed (e.g., Turkey earthquake 1999)

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Drug Interactions and Statin-Induced Rhabdomyolysis

High-Risk Statin Drug Interactions

Statin Risk Stratification

Management of Statin-Induced Rhabdomyolysis

1. Stop the statin immediately
2. Treat rhabdomyolysis as per protocol
3. Document the event for future reference
4. After recovery: Cardiology/GP discussion on risk-benefit of resuming statins
5. If rechallenge considered: Use low-interaction statin (pravastatin, rosuvastatin) at lower dose
6. Consider alternate lipid-lowering therapy (ezetimibe, PCSK9 inhibitors)

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Paediatric Rhabdomyolysis

Common Causes in Children

Key Differences from Adults

• Viral myositis is the most common cause (influenza-associated benign acute childhood myositis)
• Lower threshold to consider inherited metabolic myopathies in recurrent cases
• Weight-based dosing essential for all medications
• Propofol infusion syndrome - avoid prolonged propofol greater than 48h or greater than 4 mg/kg/hr in PICU

Paediatric Fluid Resuscitation

Paediatric Hyperkalemia Treatment

When to Investigate for Metabolic Myopathy

• Recurrent unexplained rhabdomyolysis
• Rhabdomyolysis after mild exertion
• Family history of myopathy or sudden death
• Associated hypoglycemia or cardiomyopathy
• Failure to thrive or developmental delay

Workup:

• Acylcarnitine profile
• Urine organic acids
• Muscle biopsy for histology and enzyme analysis
• Genetic testing (CPT-II, VLCAD, McArdle)
• Referral to metabolic/genetics specialist

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Quality Improvement and Audit

Key Performance Indicators for Rhabdomyolysis Management

Documentation Essentials

• Admission CK and peak CK
• Hourly urine output for first 24 hours
• Time to achieve target UO (200-300 mL/hr)
• Cause identified and documented
• Complications (AKI, hyperkalemia, compartment syndrome)
• Disposition and follow-up plan

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Patient Information

What is Rhabdomyolysis?

Rhabdomyolysis is a condition where damaged muscle releases its contents into the bloodstream. This can cause kidney problems and dangerous changes in your blood chemistry.

Warning Signs to Return to Hospital

Return to the emergency department immediately if you experience:

• Dark "cola-colored" urine returning
• Decreased urine output (passing very little urine)
• Muscle pain worsening
• Swelling of arms or legs
• Palpitations or irregular heartbeat
• Shortness of breath
• Confusion or drowsiness

Recovery Advice

1. Stay well hydrated - drink at least 2-3 liters of water daily
2. Avoid strenuous exercise until cleared by your doctor
3. Attend follow-up appointments - blood tests are needed to check kidney function
4. Tell future doctors about this episode, especially before surgery or if prescribed new medications
5. If caused by medication, do not restart without medical advice

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#compartment-syndrome #crush-injury #dialysis #fluid-resuscitation
#indigenous-health #remote-medicine #fellowship-written #fellowship-osce

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Last updated: 2026-01-24 Citation Count: 36 PMIDs